Prognosefaktoren des perinatalen Kurzzeitergebnisses bei schwerer Plazentainsuffizienz mit dopplersonografisch enddiastolischem Null- und Rückfluss in der Art. umbilicalis

Zusammenfassung

Die ausgeprägte Plazentainsuffizienz mit dopplersonografisch nachweisbarem enddiastolischem Null- oder Rückfluss (absent or reversed enddiastolic velocity, AREDV) in der Art. umbilicalis ist assoziiert mit einer hohen Morbidität und Mortalität. Die Analyse der Flusskurve des Ductus venosus soll helfen, intrauterin bedrohte Feten zu selektieren. 58 Hochrisikoschwangerschaften mit umbilikalem AREDV wurden dopplersonografisch seriell untersucht (n=364). Wir prüften die Korrelation des perinatalen Ergebnisses (Normoblastenzahl/100 Leukozyten, pH, BaseExcess, Apgarwerte) inklusive Kurzzeitmorbidität (Intubationsnotwendigkeit, Beatmungsdauer, Nachweis von RDS (respiratory distress syndrome), BPD (bronchopulmonary dysplasia), NEC (necrotising enterocolitis), IVH III+IV (intraventricular haemorrhage grade III and IV)) mit der Analyse der abgeleiteten Flusskurven (normale oder erhöhte Pulsatilität, enddiastolischer Null-oder Rückfluss) in Arteria umbilicalis (AU), Arteria cerebri media (ACM) und Ductus venosus (DV) und untersuchten den Einfluss von Geburtsgewicht und Schwangerschaftsalter. Die mittlere Beobachtungzeit betrug 12,8 Tage, 48% der Feten zeigten eine auffällige DV-Flusswelle, 26% einen venösen AREDV. Das mittlere Schwangerschaftsalter bei Geburt betrug 30 Wochen, das mittlere Geburtsgewicht 816 g. 93% der Kinder wurden lebend geboren, 12% verstarben postnatal. Die Normoblastenzahl als chron. Hypoxiemarker, nicht jedoch Parameter der postnatalen Morbidität (BPD, NEC, IVH III◦+IV◦) oder die postnatale Mortalität korrelierten in unserem Gesamtkollektiv signifikant mit den beschriebenen Alterationen arterieller oder venöser Dopplerparameter; 10 min Apgar-Wert, Nabelschurarterien-pH und –BE nur mit Veränderungen der DV-Flusskurve. „Gesundes“ Überleben beginnt, unabhängig von der Alteration arterieller oder venöser Blutflusskurven ab 27+0 Schwangerschaftswochen. Zwischen 27+0 und 30+6 Schwangerschaftswochen überlebten deutlich mehr Kinder gesund bei entsprechend weniger alterierten Flussmustern. Ein Geburtsgewicht von 590 g (Sensitivität 62,5%; Spezifität 93,5%) und ein Gestationsalter von 28+5 SSW (Sensitivität 87,5%; Spezifität 90,3%) wurden als optimale Trennschwelle zwischen gesundem Überleben und Überleben mit schwerer Erkrankung ermittelt. Unsere Ergebnisse unterstreichen die Bedeutung der Dopplersonografie, bekräftigen aber insbesondere auch die Bedeutung der Berücksichtigung des Schwangerschaftsalters bei der Festlegung des Entbindungszeitpunktes.

Abstract

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Schlüsselwörter

Doppler-Ultraschall - fetale Überwachung - intrauterine Wachstumsrestriktion - Ductus venosus - perinatales Ergebnis - Plazentainsuffizienz

Key words

Doppler ultrasound - foetal monitoring - intrauterine growth restriction - ductus venosus - perinatal outcome - placental insufficiency

• Literatur

• 1 Alfirevic Z, Stampalija T, Gyte GM. Fetal and umbilical Doppler ultrasound in high risk pregnancies. Cochrane Database Syst Rev 2010; CD007529 DOI: 10.1002/14651858.CD007529.pub2.
• 2 Kiserud T. Fetal venous circulation – an update on hemodynamics. J Perinat Med 2000; 28: 90-96
• 3 Grivell RM, Alfirevic Z, Gyte GM et al. Antenatal cardiotocography for fetal assessment. The Cochrane Database Syst Rev. 2012; 12 CD007863 DOI: 10.1002/14651858.CD007863.pub.3.
• 4 Steiner H, Schneider KTM Hrsg Dopplersonografie in Geburtshilfe und Gynäkologie. 3. Auflage Berlin: Springer Medizin; 2012: 204-214
• 5 Baschat AA. Fetal responses to placental insufficiency: An update. BJOG 2004; 111: 1031-1041
• 6 Nicolaides KH, Bilardo CM, Soothill S et al. Absence of end-diastolic frequencies in umbilical artery: a sign of fetal hypoxia and acidosis. Br Med J 1988; 297: 1026-1027
• 7 Arduini D, Rizzo G, Romanini C. The development of abnormal heart rate patterns after absent enddiastolic velocity in umbilical artery: analysis of risk factors. Am J Obstet Gynecol 1993; 168: 43-50
• 8 The GRIT Study Group . When do obstetricians recommend delivery for a high-risk preterm growth-retarded fetus?. Europ Journ Obstet Gynecol Reproduct Biol 1996; 67: 121-126
• 9 Müller T, Nanan R, Rehn M et al. Arterial and ductus venosus Doppler in fetuses with absent or reverse end-diastolic flow in the umbilical artery: correlation with short-term perinatal outcome. Acta Obstet Gynecol Scand 2002; 81: 860-866
• 10 Müller T, Nanan R, Rehn M et al. Arterial and Ductus venosus Doppler in Fetuses with Absent or Reverse End-Diastolic Flow in the Umbilical Artery: Longitudinal Analysis. Fetal Diagn Ther 2003; 18: 163-169
• 11 Baschat AA, Cosmi E, Bilardo CM et al. Predictors of neonatal outcome in early onset placental dysfunction. Obstet Gynecol 2007; 109: 250-261
• 12 Jobe AH, Bancalari E. Bronchopulmonary Dysplasia. Am J Respir Crit Care Med 2001; 163: 1723-1729
• 13 Papile LA, Burstein J, Burstein R et al. Incidence and evolution of subepenymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500gm. J Pediatr 1978; 92: 529-534
• 14 Karsdorp VH, van Vugt JM, van Geijn HP et al. Clinical significance of absent or reversed end diastolic velocity waveforms in umbilical artery. Lancet 1994; 344: 1664-1668
• 15 Zelop CM, Richardson DK, Heffner LJ. Outcomes of severely abnormal umbilical artery Doppler velocimety in structurally normal singleton fetuses. Obstet Gynecol 1996; 87: 434-438
• 16 Kurkinen-Räty M, Kivelä A, Jouppila P. The clinical significance of an absent end-diastolic velocity in the umbilical artery detected before the 34^th week of pregnancy. Acta Obstet Gynecol Scand 1997; 76: 398-404
• 17 Ertan AK, Tanriverdi AH, Hendrik J et al. Comparison of perinatal outcomes in fetuses with reverse or absent end-diastolic flow in the umbilical artery and/or fetal descending aorta. J Perinat Med 2003; 31: 307-312
• 18 Schwarze A, Gembruch U, Krapp M et al. Qualitative venous Doppler flow waveform analysis in preterm intrauterine growth-restrictes fetuses with ARED flow in the umbilical artery – correlation with short-term outcome. Ultrasound Obstet Gynecol 2005; 25: 573-579
• 19 Shand AW, Hornbuckle J, Nathan E et al. Small for gestational age preterm infants and relationship of abnormal umbilical artery Doppler blood flow to perinatal mortality and neurodevelopmental outcomes. ANZJOG 2009; 49: 52-58
• 20 Nicolini U, Nicolaidis P, Fisk NM et al. Limited role of fetal blood sampling in prediction of outcome in intrauterine growth retardation. Lancet 1990; 336: 768-772
• 21 Snijders RJM, Abbas A, Melby O et al. Fetal plasma erythropoietin concentration in severe growth retardation. Am J Obstet Gynecol 1993; 168: 615-619
• 22 Korst LM, Phelan JP, Ahn MO et al. Nucleated red blood cells: an update on the marker for fetal asphyxia. Am J Obstet Gynecol 1996; 175: 842-846
• 23 Buoncore G, Perrone S, Gioia D et al. Nucleated red blood cell count at birth as an index of perinatal brain damage. Am J Obstet Gynecol 1999; 181: 1500-1555
• 24 Baschat AA, Gembruch U, Reiss I et al. Neonatal nucleated red blood cell counts in growth-restricted fetuses: Relationship to arterial and venous Doppler studies. Am J Obstet Gynecol 1999; 181: 190-195
• 25 Hecher K, Bilardo CM, Stigter RH et al. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study. UOG 2001; 18: 564-570
• 26 Baschat AA, Gembruch U, Reiss I et al. Relationship between arterial and venous Doppler and perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol 2000; 16: 407-413
• 27 Baschat AA, Kush M, Berg C et al. Hematologic profile of neonates with growth restriction is associated with rate and degree of prenatal Doppler deterioration. Ultrasound Obstet Gynecol 2013; 41: 66-72
• 28 Hartung J, Kalache KD, Heyna C et al. Outcome of 60 neonates who had ARED flow prenatally compared with a matched control group of apropriate-for-gestational age preterm neonates. Ultrasound Obstet Gynecol 2005; 25: 566-572
• 29 Baschat AA, Gembruch U, Viscardi RM et al. Antenatal Prediction of intraventricular hemorrhage in fetal growth restriction: what is the role of Doppler. Ultrasound Obstet Gynecol 2002; 19: 334-339
• 30 Manogura AC, Turan O, Kush ML et al. Predictors of necrotising enterocolitis in preterm growth-retstricted neonates. Am J Obstet Gynecol 2008; 198: 638.e1-638.e5
• 31 Baschat AA. Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol 2011; 37: 501-514
• 32 Voßbeck S, de Camargo OK, Grab D et al. Neonatal and neurodevelopmental outcome in infants born before 30 weeks of gestation with absent or reversed end-diastolic flow velocities in the umbilical artery. Eur J Pediatr 2001; 160: 128-134
• 33 Valcamonico A, Accorsi P, Battaglia S et al. Absent or reverse end-diastolic flow in the umbilical artery: intellectual development at school age. Eur J Obstet Gynecol Reprod Biol 2004; 114: 23-28
• 34 Baschat AA, Viscardi RM, Hussey-Gardner B et al. Infant neurodevelopment following fetal growth restriction: relationship with antepartum surveillance parameters. Ultrasound Obstet Gynecol 2009; 33: 44-50
• 35 Schreuder AM, McDonnell M, Gaffney G et al. Outcome at school age following antenatal detection of absent or reversed end diastolic flow velocity in the umbilical artery. Arch Dis Child Fetal Neonatal Ed 2002; 86: F108-F114
• 36 Kaponis A, Harada T, Makrydimas G et al. The Importance of Venous Doppler Velocimetry for Evaluation of Intrauterine Growth Restriction. J Ultrasound Med 2011; 30: 529-545
• 37 Rizzo G, Capponi A, Talone PE et al. Doppler indices from inferior vena cava and ductus venosus in predicting pH and oxygen tension in umbilical blood at cordocentesis in growth-retarded fetuses. Ultrasound Obstet Gynecol 1996; 7: 401-410
• 38 Soothill PW, Ajayi RA, Campbell S et al. Relationship between fetal acidemia at cordocentesis and subsequent neurodevelopment. Ultrasound Obstet Gynecol 1992; 2: 80-83
• 39 Alves SKA, Francisco RPV, Miyadahira S et al. Ductus venosus Doppler and postnatal purcomes in fetuses with absent or reversed end-diastolic flow in the umbilical arteries. Europ J Obstet Gynecol Reprod Biol 2008; 141: 100-103
• 40 Cosmo YC, Araujo E, Moreira de Sa RA et al. Doppler velocimetry of ductus venosus in preterm fetuses with brain sparing effect: neonatal outcome. Journ Perinat Med 2012; 6: 40-46
• 41 Morris RK, Selman TJ, Verma M et al. Systematic review and meta-analysis of the test-accuracy of Ductus venosus Doppler to predict compromise of fetal/neonatal wellbeing in high risk pregnancies with placental insufficiency. Eur J Obstet Gynecol Reprod Biol 2010 152: 3-12 DOI: 10.1016/j.ejogrb.2010.04.017. Review
• 42 Chalubinsky KM, Repa A, Stammler-Safar M et al. Impact of Doppler sonography on intrauterine management and neonatal outcome in preterm fetuses with intrauterine growth restriction. Ultrasound Obstet Gynecol 2012; 39: 293-298
• 43 Cruz-Lemini M, Crispi F, Mieghem T et al. Risk of Perinatal Death in Early-Onset Intrauterine Growth Restriction according to gestational Age and Cardiovascular Doppler Indices: A Multicenter Study. Fetal Diagn Ther 2012; 32: 116-122
• 44 GRIT Study Group . A randomised trial of timed delivery for the compromised preterm fetus: short term outcomes and Bayesian interpretation. BJOG 2003; 100: 27-32
• 45 GRIT Study Group . Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentered randomised controlled trial. Lancet 2004; 364: 513-520
• 46 Turan OM, Turan S, Berg C et al. Duration of persistent abnormal ductus venosus flow and its impact on perinatal outcome in fetal growth restriction. Ultrasound Obstet Gynecol 2011; 38: 295-302
• 47 Baschat AA, Odibo AO. Timing of delivery in fetal growth restriction and childhood development: some uncertainties remain. Am J Obstet Gynecol 2011; 204: 2-3